Abstract/Details

Structure of MfdN and its influence on the stability and activity of the MFD protein


2009 2009

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Abstract (summary)

Damage to actively transcribed genes is repaired at a faster rate than damage to non-transcribed genes due to the activity of proteins called transcription repair coupling factors. These proteins recognize RNA polymerases that have stalled on damaged DNA, remove them, and recruit DNA repair proteins to the site of the damage. In bacteria one protein performs all of those functions, Mfd. We are investigating the regulation of Mfd's activity and we hypothesize that the opening and closing of the interface between the protein's two principal domains, MfdN (residues 1-450) and MfdC (residues 473-1148), toggles Mfd between active and inactive states. We have solved the crystal structure of MfdN by molecular replacement. Its structure superimposes well with that same region from the crystal structure of the full length Mfd protein (Deaconescu et al 2006), with an rmsd of 1.1 Å. The fold of MfdN appears to be independent of MfdC and the linker region (451-472), which is too disordered to be seen in the crystal structure. We have probed the stability of the N and C terminal regions of Mfd expressed as separate constructs, and the effect of disrupting the interface between them on the properties of Mfd. We believe that MfdN exerts a stabilizing influence on structure of full length Mfd, and that it has an inhibitory effect on the protein's activity through its binding interactions with MfdC.

Indexing (details)


Subject
Biochemistry
Classification
0487: Biochemistry
Identifier / keyword
Pure sciences, DNA repair, MFD protein, TC-NER, Transcription-repair coupling factor, UvrB
Title
Structure of MfdN and its influence on the stability and activity of the MFD protein
Author
Murphy, Michael N.
Number of pages
200
Publication year
2009
Degree date
2009
School code
0118
Source
DAI-B 70/03, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9781109059441
Advisor
Theis, Karsten W.
Committee member
Hardy, Jeanne A.; Martin, Craig T.; Thompson, Lynmarie K.
University/institution
University of Massachusetts Amherst
Department
Chemistry
University location
United States -- Massachusetts
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3349734
ProQuest document ID
304920602
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/304920602
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